Dunne B M, McNamara M, Clynes M, Shering S G, Larkin A M, Moran E, Barnes C, Kennedy S M
National Ophthalmic Pathology Laboratory, Royal Victoria Eye & Ear Hospital, Dublin, Ireland.
Hum Pathol. 1998 Jun;29(6):594-8. doi: 10.1016/s0046-8177(98)80008-7.
Metastatic uveal melanoma is profoundly chemoresistant and has a very poor outcome. We have previously shown that the MDR1 gene and its gene product P-glycoprotein (P-gp), which are known to cause drug resistance in cancer cells, are expressed in ocular melanoma. Overexpression of MDR1 has been associated with a poor survival in some tumor types treated by chemotherapy and in some untreated tumours. To assess whether MDR1 expression is of prognostic value in uveal melanoma, we evaluated the expression of MDR1 by immunohistochemistry in 108 cases. Three semiquantitative grades were used to evaluate positive staining. We detected MDR1 expression in 80% of cases; 28% showed grade I staining; 30%, grade II staining; and 22%, grade III staining. There was a statistically significant association (P=.004) between MDR1 expression by tumor cells and shorter survival times (n=96), which was most striking at grade III levels of expression. Multivariate analysis showed that MDR1 expression is an independent prognostic indicator of poor survival. We conclude that (1) MDR1 may be involved in chemoresistance and tumor propagation in primary uveal melanoma, and (2) increasing levels of expression are prognostically significant and may prove a useful marker of tumor invasiveness, independent of established prognostic factors.
转移性葡萄膜黑色素瘤具有很强的化疗耐药性，预后很差。我们之前已经表明，已知可导致癌细胞耐药的MDR1基因及其基因产物P-糖蛋白（P-gp）在眼黑色素瘤中表达。MDR1的过表达与某些接受化疗的肿瘤类型以及某些未接受治疗的肿瘤的不良生存相关。为了评估MDR1表达在葡萄膜黑色素瘤中是否具有预后价值，我们通过免疫组织化学对108例病例评估了MDR1的表达。采用三个半定量等级来评估阳性染色。我们在80%的病例中检测到MDR1表达；28%显示I级染色；30%显示II级染色；22%显示III级染色。肿瘤细胞的MDR1表达与较短的生存时间（n = 96）之间存在统计学显著关联（P = 0.004），这在III级表达水平最为明显。多变量分析表明，MDR1表达是不良生存的独立预后指标。我们得出结论：（1）MDR1可能参与原发性葡萄膜黑色素瘤的化疗耐药和肿瘤增殖，（2）表达水平的增加具有预后意义，可能证明是肿瘤侵袭性的有用标志物，独立于既定的预后因素。
